Erythrocytic metabolic defects associated with low or unstable glutathione are probably the most prevalent of the inherited red cell disorders. Their clinical manifestations range from drug-induced hemolytic anemia to congenital nonspherocytic hemolytic disease. The objective of the proposed research is to evaluate glutathione-deficiency in sheep erythrocytes (gamma-glutamylcysteine synthetase deficiency) as a model for the erythrocytic metabolic defects in humans associated with this group of disorders. The glutathione synthesizing enzymes will be purified and their kinetic characteristics evaluated. Therapeutic alteration of glutathione levels will be attempted. The effects of glutathione deficiency on the oxygen-hemoglobin dissociation curve and the genetic control of effected enzymes will be studied. Study of these animals may lead to therapy which can be used in treatment of human disorders involving erythrocyte glutathione.